Anti-ST2 (MSTT1041A) in COPD (COPD-ST2OP)

Where a COPD exacerbation is defined by symptomatic worsening of COPD requiring:

• Use of systemic corticosteroids for at least 3 days; a single depot injectable dose of corticosteroids will be considered equivalent to a 3-day course of systemic corticosteroids; and/or
• Use of antibiotics and/or
• inpatient hospitalisation or death due to COPD

Number of Participants with Adverse Events in the 48 Weeks of the Trial From First Dose

Number of Participants with Serious Adverse Events in the 48 Weeks of the Trial From First Dose

Patient reported outcome (PRO). To evaluate health status; designed to measure health impairment in patients with asthma and COPD. It is in two parts. Part I produces the Symptoms score, and Part 2 the Activity and Impact scores. A Total score is also produced. The Total score is calculated by summing the weights to all the positive responses in each component. This score is then put onto the scale 0 to 100 by dividing by the Total possible sum (3201.9)- and times by 100. A score of 0 would represent the best health and a score of 100 would represent the worst possible state of the patient.

Patient reported outcome (PRO). To evaluate health status: evaluation and rehabilitation education guidance on the respiratory and motor functions of patients with chronic obstructive pulmonary disease. CAT score is made by summing the score to eight questions on COPD. For each, the person with COPD picks the number between 0-5 that reflects their response. A zero indicates no effect on quality of life, whereas a 5 suggests a very significant effect.The CAT has a scoring range of 0-40, with 40 indicating the most severe COPD and 0 being the least severe COPD.

A change of 2 units suggests a meaningful difference. This test should be used in conjunction with the mMRC and forced expiratory volume in one second (FEV1) to determine COPD health assessment of participants.

Patient reported outcome (PRO). To evaluate respiratory breathlessness symptoms (Grade 0-4, with Grade 0 being breathlessness with strenuous exercise to Grade 4 being breathlessness for daily activities like dressing).

Patient reported outcome (PRO). To evaluate respiratory symptoms. The participant is asked to place a mark (X) on the scale at the point that best describes their health currently. Minimum score 0mm (better outcome), maximum score 100mm (worse outcome) for each section of the scale (dyspnoea, cough, sputum). The Total VAS score is the sum of the 3 scales, thus the minimum score is 0 (best outcome) and the maximum 300 (worst outcome).

The sputum purulence colour card using the Bronko test has values of 0, 1, 2, 3, 4, 5 and 6. Lower scores indicate better health.

To assess lung function. The participant will take a maximum inhalation, release maximum exhalation and then continue to exhale afterwards. They will then be treated with a bronchodilator. The spirometry test is then repeated to determine how much the bronchodilator medication helped with breathing. FEV1/FVC ratio will be calculated.

To assess lung function. FEV1 is the volume of air that can forcibly be blown out in first 1 second, after full inspiration. Post BD Forced Expiratory Volume in 1 Second (FEV1)

To assess lung function, i.e. the functional residual capacity of the lungs. The participant sits inside an airtight box, inhales or exhales to a particular volume (usually FRC), and then a shutter drops across their breathing tube. The participant makes respiratory efforts against the closed shutter, causing their chest volume to expand and decompressing the air in their lungs. The increase in their chest volume slightly reduces the box volume (the non-person volume of the box) and thus slightly increases the pressure in the box. Total Lung Capacity and Residual Volume measured.

To assess inflammation at exacerbation events. White blood cells, eosinophils and neutrophils will be measured.

To assess inflammation at exacerbation events. Eosinophils cells will be measured.

To assess lung function. The participant will take a maximum inhalation, release maximum exhalation and then continue to exhale afterwards. They will then be treated with a bronchodilator. The spirometry test is then repeated to determine how much the bronchodilator medication helped with breathing. FEV1 and FVC will be measured.

To assess lung function. The participant will take a maximum inhalation, release maximum exhalation and then continue to exhale afterwards. They will then be treated with a bronchodilator. The spirometry test is then repeated to determine how much the bronchodilator medication helped with breathing. FEV1 % predicted and FVC % predicted will be measured.

To assess lung function, i.e. the functional residual capacity of the lungs. The participant sits inside an airtight box, inhales or exhales to a particular volume (usually FRC), and then a shutter drops across their breathing tube. The participant makes respiratory efforts against the closed shutter, causing their chest volume to expand and decompressing the air in their lungs. The increase in their chest volume slightly reduces the box volume (the non-person volume of the box) and thus slightly increases the pressure in the box. Residual Volume/Total Lung Capacity ratio will be calculated. RV/TLC ratio: this is the residual volume (RV) to total lung capacity (TLC). It is calculated as a percentage as follows: RV/TLC ×100.

To assess inflammation at exacerbation events. Sputum inflammatory cell differentials: Macrophages

To assess inflammation at exacerbation events. Epithelium cells will be measured.

Quantitative measures of airway geometry and densitometry. Mean lung density expiratory/inspiratory [MLD E/I] (small airway), % wall area [WA] and LA (larger airways) will be measured.

Various biomarkers of inflammation will be measured in sputum.

Various biomarkers of inflammation will be measured in blood.

ILC2 cells will be analysed using plasma for biomarkers.

Various biomarkers of inflammation will be measured in urine.

Mediators of inflammation in blood, sputum and urine will be assessed.

To assess upper airway inflammation. This is a non-invasive method to sample nasal mucosal lining fluid using a synthetic absorptive matrix (SAM) of low protein binding. The SAM is advanced up the lumen of the nasal cavity, and then the outside of the nose is gently pressed to oppose the SAM against the nasal mucosa for 30 seconds.

To assess airway upper inflammation. Nasal epithelial cells will be sampled from the anterior nares using either a polyester swab or a cytology brush with the standard collection method - cytology brush sampling from beneath the inferior turbinate. This test is optional for participants.

To assess inflammation. PTR-MS, ADVION and ReCIVA will be used to measure gaseous molecules found in the breath that are from inside and outside the lungs. We aim to collect these molecule and analyse them to see if there are any changes in a persons breath that could be linked to the metabolic health, before, during and after taking the drug or placebo.

To assess airway infection and ecology. We will analyse the microbes in patients' lungs using their sputum samples and profile the effect of treatment on these microbes.

To assess airway infection and ecology. We will analyse the microbes in patients' lungs and profile the effect of treatment on these microbes.

To evaluate the rate of protocol-defined COPD exacerbations through 48 weeks treatment period, patient reported outcomes (PROs), and lung functions, by subgroup outcomes.

To evaluate the efficacy of anti-ST2 versus placebo on the outcome rate of protocol-defined COPD exacerbations through 48 weeks treatment period, patient reported outcomes (PROs) and lung function in subgroups defined by baseline blood eosinophil count.

To evaluate the efficacy of anti-ST2 versus placebo on the outcome rate of protocol-defined COPD exacerbations through 48 weeks treatment period, patient reported outcomes (PROs) and lung function in subgroups defined by baseline blood eosinophil count.

To evaluate the efficacy of anti-ST2 versus placebo on the outcome rate of protocol-defined COPD exacerbations through 48 weeks treatment period, patient reported outcomes (PROs) and lung function in subgroups defined by baseline blood eosinophil count.